11種類の腫瘍における癌の移行時の表遺伝子調節
Nadezhda V Terekhanova1,2, Alla Karpova1,2, Wen-Wei Liang1,2
1Department of Medicine, Washington University in St Louis, St Louis, MO, USA.
Nature
|November 2, 2023
まとめ
この研究は100万以上の細胞を分析することで 癌の発症と転移の主要な表遺伝的要因を明らかにしました この発見は,癌の進行における表遺伝的変化,遺伝子発現,遺伝的要因の相互作用を強調しています.
科学分野:
- ゲノミクス
- エピジェネティクス
- 癌 生物学
背景:
- クロマチンのアクセシビリティは 遺伝子発現と細胞のアイデンティティを制御し 癌を理解する上で極めて重要です
- クロマチンのアクセシビリティの変化は,がんの発症,進行,転移に関与しています.
- 腫瘍性変異のエピジェネティックな要因は 遺伝的要因と比較して 解明されていない.
研究 の 目的:
- パン癌のエピジェネティックとトランスクリプトミックのアトラスを構築する.
- 単核クロマチンのアクセシビリティとRNAシーケンシングデータを用いて,癌の移行に関連したエピジェネティック・ドライバーを特定する.
- 強化剤のアクセシビリティと遺伝子発現の相関性を調査し,エピジェネティックと遺伝的誘導因子の協力関係を明らかにする.
主な方法:
- 225個のがんサンプルでトランポゼーゼアクセシブルクロマチン (snATAC-seq) の単核測定法を使用した.
- 206個のサンプルから得られた単細胞または単核RNAシーケンシング (sc/snRNA-seq) データと統合されたsnATAC-seqデータ.
- 100万以上の細胞を分析し,アクセス可能なクロマチン領域,転写因子モチーフ,レギュロンなどを特定した.
主要な成果:
- 一般的およびがん特異的な表遺伝因子 (例えば,ABCC1,VEGFA,GATA6,FOXファミリーモチーフ,FGF19,ASAP2,EN1,PBX3モチーフ) を特定した.
- TP53,低酸素,TNF信号などの特定の経路が癌の発症と関連しています.
- 関連するエストロゲン反応,上皮-メゼンキーマ移行,および転移経路の頂点結節.
- 強化剤のアクセシビリティと遺伝子発現の強い相関関係と,表遺伝的および遺伝的要因の協力関係を明らかにした.
結論:
- 構築されたアトラスは,がんにおける表遺伝子動態の調査のための基盤を提供します.
- エピジェネティック・ドライバは癌の発症,進行,転移において重要な役割を果たします.
- エピジェネティックと遺伝的要因の相互作用を理解することは 癌の研究にとって極めて重要です
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